Type 2 Diabetes (T2D) is an inflammatory disease affecting 26 million people in the US (11%) and is predicted to affect more than 30% of adults in the US by 2050. The economic cost of T2D is over $200 billion a year. People with T2D suffer from hyperglycemia due to low insulin production, poor transport of insulin, or cellular resistance to insulin which can lead to retinopathy, nephropathy, neuropathy, and cardiovascular disease. Chronic inflammation in T2D is a leading cause of the progression of the disease. Obesity, also occurring at epidemic rates in the US, causes chronic low- grade inflammation thus contributing to T2D. Although current therapies can maintain glucose control and reduce insulin resistance, complications associated with chronic inflammation and organ damage drive the effort to develop drugs targeting specific steps in the inflammatory cascade. We propose that natural products have the potential to fill this therapeutic gap while reducing potential side effects and compensatory reactions requiring secondary treatment. To combat the inflammation that leads to T2D and its complications, we developed two naturally derived products: WG0401 and WG0301, which are both proprietary, novel, well-characterized, bioactive enhanced natural extracts. Both extracts show strong effects against inflammation as demonstrated in human cell-based bioassays and animal models of inflammation. Both were well tolerated in humans in previously conducted clinical trials and can be Generally Regarded As Safe (GRAS), thereby reducing the time and expense of getting a product to market. Our goal is to develop a novel, effective medical food to control the underlying pathological effects of chronic inflammation that lead to T2D. Aim 1. Demonstrate that WG0401 and WG0301 will reduce inflammatory metabolites that lead to complications of T2D. Biomarkers for T2D and inflammatory metabolites that play major roles in T2D will be measured in the Zucker diabetic fatty rat animal model of T2D that have been treated with WG0401 or WG0301. Successful results will show statistically significant improvement within treatment groups or between controls and treated rats. Aim 2. We propose that the inhibition of inflammatory genes reduces the metabolites measured in Aim 1. We will measure correlations between the gene products and the down-regulation of inflammatory metabolites and/or biomarkers for inflammation and T2D by WG0401 and WG0301 and compare to metformin and ibuprofen. Observation of a positive correlation supports our hypothesis. Aim 3. Select one of the two products based on the results above for further development. Successful completion of this project will enable the design and initiation of clinical trials in Phase II, using one of our extracts for the management of T2D.